Method of remineralizing teeth

ABSTRACT

A method of remineralizing teeth by using an oral hygiene composition comprising a polyvinyl acetal diethylaminoacetate and a fluoride ion-feeding compound; and the composition for use in the method.

FIELD OF THE INVENTION

The present invention relates to an oral composition effective forremineralizing teeth, and a method for using the same.

BACKGROUND OF THE INVENTION

In an oral cavity, there is an equilibrium state in which a constituentingredient of teeth, hydroxy apatite, dissolves from the teeth, and acalcium ion or a phosphate ion in a saliva deposits onto the toothsurface. Due to this equilibrium state, the tooth surface is alwayschanging. When the equilibrium moves towards the dissolution of hydroxyapatite, a white spot develops on the tooth surface, which leads to acaries-inducing state referred to as demineralization. When theequilibrium moves towards the reformation of a demineralized enamel fromhydroxy apatite, which is referred to as remineralization, caries can beprevented or treated by the remineralization.

A major factor governing the equilibrium is a saturation degree ofhydroxy apatite in the oral cavity. That is, when hydroxy apatitebecomes supersaturated, the remineralization occurs. Reversely, when thesaturation degree of hydroxy apatite is lowered, the demineralizationoccurs. Since hydroxy apatite dissolves in an acid, in an acidic region,the saturation degree is lowered and the demineralization occurs.

Thus, there has been proposed an oral composition into which hydroxyapatite and calcium compounds, constituent ingredients thereof areblended and which promotes the remineralization.

For example, there is described that the remineralization is promoted byusing certain hydroxy apatite in JP-A 55-57514, tetra-calcium phosphatein JP-A 1-71807, or amorphous calcium phosphate in U.S. Pat. No.5,562,895. There is described a composition with added soluble calciumphosphate containing calcium and phosphate in the ionized state in JP-A8-319224, and there is described a toothpaste containing silica anddicalcium phosphate in JP-A 8-502988 (WO 94/10969).

For the remineralization, it is also known that fluoride ion-feedingcompounds release a fluoride ion to promote a remineralization processand, thereby, reduce caries that has previously been existed within atooth structure. For example, there are proposed a combination ofxylitol and a fluoride in U.S. Pat. No. 371,145, and a combination ofhydroxy apatite and a fluoride in JP-A 1-110608. However, although acertain effect has been recognized for the primary teeth, a productwhich can be said to be sufficient for remineralizing the second teethhas not been developed yet.

By the way, it has been hitherto known that a fluoride ion reinforces adentine. Thus, an attempt to enhance the caries preventing effect hasbeen tried by intensifying such an action of a fluoride ion. In JP-A63-246316, pyridoxine derivatives are blended into an oral compositionfor the purpose of promoting uptake of a fluoride ion and improving anacid-resistant property of the teeth. There is proposed a poly-cationicpolymer in JP-A 3-5417. However, none of them disclose theremineralizing action.

The previous methods, which employ a composition into which hydroxyapatite is blended or an oral composition into which a fluoride isblended, can not accomplish the desired effect on the teeth under anoral cavity environment where the teeth are easily demineralized, or onthe teeth which has already begun to be demineralized. Also, there is alimitation that a pH of a formulation as an oral composition is requiredto adjust to a higher pH than that of a weak acid because when the oralcavity is made acidic, the demineralization is caused.

An object of the present invention is to enhance the effects ofpreventing or treating caries of an enamel or root surface, or dentinhyperesthesia, by promoting the ability of fluorine to remineralize.

SUMMARY OF THE INVENTION

The present inventors extensively studied the promotion of theremineralizing action of a fluoride ion and, as a result, found thatpolyvinyl acetal diethylaminoacetate has an excellent remineralizingaction promoting effect. Polyvinyl acetal diethylaminoacetate wasdeveloped as a coating agent for tablets, and, for instance, there isreported in JP-A 5-339136 that it is effective for suppressing dentalplaque accumulation or promoting adsorption of a fluoride onto the toothsurface. However, its remineralizing action promoting effect is notknown.

Also, the present inventors found that even when a pH of an oralcomposition is adjusted to an acidic region of about 3-6.5, thedemineralization is not caused, and, unexpectedly, the remineralizingaction promoting effect is remarkably improved than in a neutral region.Moreover, the present inventors found that the remineralizing actionpromoting effect is also improved by blending an anionic surfactanttherein.

The present invention was completed based on such novel findings and inone aspect thereof, provides a method of remineralizing teeth whichcomprises using an oral composition comprising polyvinyl acetaldiethylaminoacetate and a fluoride ion-feeding compound which feeds afluoride ion. This oral composition may further contain an anionicsurfactant.

In an another aspect, the present invention provides an oral compositionfor remineralizing the teeth, which is used for the method of thepresent invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Polyvinyl acetal diethylaminoacetate to be used in the present inventionis an acetal produced by dehydration between polyvinyl alcohol andacetaldehyde, and which is a basic high-molecular compound in which apart of the remaining hydroxyl groups are bound to diethylaminoaceticacid via an ester linkage and, for example, a commercially availableproduct such as “AEA” (Sankyo Corporation) may be used.

An amount of polyvinyl acetal diethylaminoacetate to be blended is inthe range of 0.01-10% by weight, preferably in the range of 0.02-2% byweight, from a viewpoint of the promotion of the remineralizing action.

As the fluoride ion-feeding compound which feeds a fluoride ion, thereare sodium fluoride, potassium fluoride, ammonium fluoride, calciumfluoride, copper fluoride, zinc fluoride, lithium fluoride, cesiumfluoride, zirconium fluoride, tin fluoride, sodium monofluorophosphate,potassium monofluoro-phosphate, sodium titanium fluoride, potassiumtitanium fluoride, hexylamine hydrofluoride, laurylamine hydrofluoride,cetylamine hydrofluoride, lysine hydrofluoride, glycine hydrofluoride,alanine hydrofluoride, fluorosilane and the like, and they can be usedalone or in a combination of two or more of them. In view of the oraluse, preferred are sodium fluoride, potassium fluoride, ammoniumfluoride, tin fluoride, sodium monofluorophosphate, and potassiummonofluorophosphate. An amount of the fluoride ion-feeding compound tobe blended is in the range of 10-50,000 ppm, preferably 90-20,000 ppm interms of a fluoride ion based on the total amount of the oralcomposition, from a viewpoint of the remineralizing effect. When theamount is below 10 ppm, the remineralizing action can not be expectedand, when it exceeds 50,000 ppm, the remineralization promoting effectby polyvinyl acetal diethylaminoacetate does not increase much, beingnot economical. In a method of using almost every day for a long periodof time, the concentration in the composition of 90-5,000 ppm isparticularly preferred and, in a method of using at long-term intervalsexceeding one month, 9,000-20,000 ppm is particularly preferred.

As the anionic surfactant to be used in the present invention, there aresalts of N-long chain acyl basic amino acid such as sodium salt ofN-acyl-L-glutamate, sodium salt of N-hydrogenated tallow fatty acidacyl-L-glutamate, sodium lauroyl sarcosinate, water-soluble salts ofhigher alkyl sulfate having alkyl group of 8-18 carbon atoms such assodium lauryl sulfate and sodium myristyl sulfate, polyoxyethylene alkylsulfate salt, alkylsulfoacetate salt, α-olefin sulfonate salt,sulfosuccinate derivatives, sodium salt of higher fatty acidmonoglyceride monosulfate, N-methyl-N-palmitoyltauride salts and thelike. An amount of the anionic surfactant to be blended is 0.01-10% byweight, preferably 0.1-5% by weight based on the total amount of theoral composition.

As an acid to be used for adjusting a pH of the oral composition, citricacid, malic acid, phosphoric acid, and aromatic carboxylic acids such asbenzoic acid, nicotinic acid and salicylic acid, and salts thereof areexemplified, and one or more selected from them may be used. A preferredpH range is 3-6.5. When a pH is below 3, the demineralization by an acidis remarkable and, when a pH exceeds 6.5, the effect becomes weak. Anamount of the acid to be blended is preferably 0.01-3% by weight and,when it exceeds 3% by weight, a physical property as an oral compositionbecomes unstable.

The oral composition of the present invention may be appropriatelyformulated, depending upon its use, into a form such as toothpaste,pasta, powder or liquid dentifrice, wetting dentifrice, gel, cream,mouthwash, spray, foam, coating agent and the like, according to theconventional methods. Other ingredients to be blended are notparticularly limited and the known polishing agents, humectants,thickening agents, foaming agents, preservatives, flavoring agents,therapeutic agents and the like may be blended into the oralcomposition, so long as they do not deteriorate the effects of thepresent invention.

A container may be made of compatible materials, all kinds ofdispenser-container are usable, and a laminate tube made of aluminium orplastics, a plastic container such as of squeeze-type and pumpdispenser, or an aerosol container may be used. In the case of a gel orvarnish form, the composition may be contained in a syringe.

The method of the present invention may be practiced by applying theoral composition to the demineralized portion of the tooth such as bybrushing or mouth washing. For example, in the case of a dentifrice or amouthwash, they are used one to three times a day according to theconventional using method. Usually, 0.2-1.5 g of a dentifrice or 5-20 mlof a mouthwash as a daily amount is used so that the daily amount of afluoride is 0.1-2 mg, particularly preferably approximately 1 mg.Moreover, the oral composition of the present invention may beformulated into the form such as a gel or a varnish to specificallyapply onto the demineralized portion of the teeth in a topical manner.In the case of a gel or a varnish for the topical application, it may beapplied in the frequency of once a month to once a year.

The remineralization of teeth is accomplished by the above way of usingand, thereby, the effects of preventing or treating caries, root surfacecaries and dentin hyperesthesia can be exerted.

Next, the present invention will be further illustrated by way of thefollowing Experimental Examples and Examples, which are not to beconstructed to limit the scope of the present invention. Unlessotherwise indicated, “%” represents percent (%) by weight.

EXPERIMENTAL EXAMPLE 1

An artificial caries was produced using a procedure described by D. J.White et al., Caries Research, Volume 22, page 27 (1988) and tested forthe remineralization promoting effect in vitro. Namely, a tooth wasdemineralized to its sub-surface area with a demineralizing solutioncontaining 50% saturated hydroxy apatite/0.1 M of lactic acid/pH 5.0 toproduce the artificial caries. The tooth was immersed in a treatmentsolution each time for one minute, four times a day, by simulating aconventional method for use of a dentifrice or a mouthwash. The toothwas demineralized with an acid for at least three hours a day, and wasimmersed in an artificial saliva for the remaining time. The treatmentwas repeated for eight days. Then, the tooth was cut into thin sectionsand the X-ray photograph of the sections was taken to calculate itsmineral amount. The remineralization ratio was calculated as a ratio ofthe increased mineral amount relative to the demineralized mineralamount. A greater value shows the greater remineralization. The resultsare shown in Table 1.

TABLE 1 Remin- eralization Treatment solution pH ratio Compara- Citratebuffer (0.1 M) 6.5  0 tive Example 1 Compara- Polyvinyl acetaldiethylaminoacetate 6.5  0 tive (0.1%) + Citrate buffer (0.1 M) Example2 Compara- Sodium fluoride (0.05%) + 8 31 tive Phosphate buffer (0.1 M)Example 3 Compara- Sodium fluoride (0.05%) + 6.5 30 tive Phosphatebuffer (0.1 M) Example 4 Compara- Sodium fluoride (0.05%) + 3 15 tiveCitrate buffer (0.1 M) Example 5 Example 1 Sodium fluoride (0.05%) + 6.554 Polyvinyl acetal diethylaminoacetate (0.1%) + Phosphate buffer (0.1M) Example 2 Sodium fluoride (0.05%) + 5 66 Polyvinyl acetaldiethylaminoacetate (0.1%) + Citrate buffer (0.1 M) Example 3 Sodiumfluoride (0.05%) + 3 69 Polyvinyl acetal diethylaminoacetate (0.1%) +Phosphate buffer (0.1 M) Example 4 Sodium fluoride (0.05%) + 6.5 69Polyvinyl acetal diethylaminoacetate (0.1%) + Sodium lauryl sulfate(0.1%) Example 5 Sodium fluoride (0.05%) + 6.5 68 Polyvinyl acetaldiethylaminoacetate (0.1%) + Sodium salt of N-acyl-L-glutamic acid(0.1%) Example 6 Sodium fluoride (0.05%) + 6.5 63 Polyvinyl acetaldiethylaminoacetate (0.1%) + Sodium lauroyl sarcosinate (0.1%)

These results show that, in the method of the present invention, theremineralization is caused more remarkably by adding sodium fluoridetogether with polyvinyl acetal diethylaminoacetate than by adding sodiumfluoride alone. Moreover, the results show that the remineralization iscaused even in an acidic region where the demineralization is usuallycaused and, additionally, show that the significantly excellentremineralization is accomplished by adding an anionic surfactantthereto.

EXAMPLES 7-11

A toothpaste was prepared according to the formulation in Table 2 usingthe conventional procedures.

TABLE 2 Amount (%) Comparative Example Example Ingredient 7 7 8 9 10 11Sodium fluoride 0.2 0.2 0.2 0.2 0.2 0.2 Polyvinyl acetaldiethylaminoacetate — 0.1 0.1 0.1 0.1 0.1 Polyoxyethylene hydrogenatedcastor oil — 1.0 — — — 0.5 Sodium lauryl sulfate 1.0 — — — 1.0 0.5Sodium lauroyl sarcosinate — — — 1.0 — — Sucrose fatty acid ester — —1.0 — — — Citric acid — 0.5 — — — 0.2 Sodium dihydrogenphosphate — — 0.5— — 0.2 Silicic acid anhydride 20   20   20   20   20   20   Sodiumcarboxymethyl cellulose 1.5 1.5 1.5 1.5 1.5 1.5 Saccharin sodium 0.2 0.20.2 0.2 0.2 0.2 Sorbitol 60   60   60   60   60   60   Titanium oxide0.3 0.3 0.3 0.3 0.3 0.3 Flavor 0.7 0.7 0.7 0.7 0.7 0.7 Water balancebalance balance balance balance balance pH 6.5 6.5 6.0 5.5 5.0 5.0

EXPERIMENTAL EXAMPLE 2

The dentifrice compositions of Examples 7-11 were tested in vivoaccording to the Rat Caries Assay described by R. Schmidt et al.,Journal Clinical Dentistry, Volume 1, page 75 (1989). CARA rats wereused in the test. The rats were fed with a caries-inducing food (56%sucrose, 28% skim milk) beginning on the day 25 after birth, andStreptococcus sorbinus and Actinomyces viscosus were administered twicea day on the days 25 and 26 after birth. Each 0.1 ml of dentifrices ofComparative Examples or Examples was applied once a day for twenty-onedays, and the number of initial smooth surface caries was evaluatedafter the completion of the test. The results of the assay are shown inTable 3.

TABLE 3 Average/rat N Number of initial caries Comparative Example 7 1011.2 Example 7 10 1.7 Example 8 10 1.5 Example 9 10 2.0 Example 10 102.2 Example 11 10 1.9

These results show that the development of initial caries was moreremarkably suppressed by administrating a dentifrice to which sodiumfluoride together with polyvinyl acetal diethylaminoacetate is addedthan a dentifrice to which sodium fluoride alone is added. This effectis due to the promotion of the remineralizing ability.

EXPERIMENTAL EXAMPLE 3

A clinical test was performed as essentially described by Stephen etal., International Dental Journal, Volume 44, page 287 (1994). Namely, aclinical test for human was performed on 11-12 years old children forone year. The children were directed and managed to, two to three timesaccording to the conventional method, take approximately 1 g of a testdentifrice on a toothbrush, brush the oral cavity for a few minutes and,thereafter, rinse the mouth. At the starting and ending points of thetest, inspects were performed to record the number of the tooth surfacewith a white spot and caries tooth surface, and the increased numberrelative to that at the starting point of the clinical test wascalculated. The results of the clinical test are shown in Table 4.

TABLE 4 Increased number of the white spot or N caries tooth surfaceComparative Example 7 512 3.5 Example 7 459 1.9 Example 10 507 2.2

These results show that the method of the present invention suppressedthe increase of the number of the white spot on the tooth surfaceproduced by the demineralization, and at the same time suppressed theincrease of the tooth surface caries, which was accompanied by thepromotion of the remineralizing ability.

EXAMPLE 12

A toothpaste was prepared according to the following formulation usingthe conventional procedures.

Ingredient Amount (%) Sorbitol 61.5 Xylitol 9.0 Silicic acid anhydride12.0 Carboxymethyl cellulose 0.5 Sodium polyacrylate 0.6 Sodium laurylsulfate 1.1 Polyoxyethylene hydrogenated castor oil 0.5 Polyvinyl acetaldiethylaminoacetate 0.1 Citric acid 1.5 Titanium oxide 6.5 Flavor 0.7Sodium fluoride 0.32 Purified water balance A pH was adjusted to 6.0.

Approximately 0.5 g of the present composition was applied three times aday to a child developing a white spot on the tooth surface to clean theoral for six months. The composition had an excellent remineralizationpromoting ability and, after one year, no caries developed from thewhite spot was recognized.

EXAMPLE 13

A mouthwash was prepared according to the following formulation usingthe conventional procedures.

Ingredient Amount (%) Glycerol 35.5 Propylene glycol 5.0 Sodiumpolyacrylate 3.0 Polysorbate 0.5 Sodium lauroyl sarcosinate 0.5Saccharin sodium 0.1 Polyvinyl acetal diethylaminoacetate 0.1 Malic acid0.2 Flavor 0.1 Sodium fluoride 0.05 Purified water balance A pH wasadjusted to 6.0.

A child at high risk of the development of caries was rinsed in the oralcavity with approximately 20 ml of the present composition, which wasthen disgorged. This treatment was performed, after cleaning the oralcavity, three times a day for one year. The composition of the presentinvention had an excellent remineralization promoting ability and couldprevent the development of caries.

EXAMPLE 14

A mouthwash was prepared according to the following formulation usingthe conventional procedures.

Ingredient Amount (%) Glycerol 10.5 Sodium lauryl sulfate 0.2Polyoxyethylene hydrogenated castor oil 1.0 Polyvinyl acetaldiethylaminoacetate 0.1 Phosphoric acid 0.1 Flavor 0.1 Ethanol 8.0Sodium fluoride 0.05 Xylitol 10.0 Purified water balance A pH wasadjusted to 5.5.

A person whose gingiva had retracted and whose dental root had beenexposed was rinsed in the oral cavity with approximately 10 ml of thepresent composition, which was then disgorged. This treatment wasperformed, after normally cleaning the cavity, three times a day for sixmonths. The present composition had an excellent remineralizationpromoting ability and root surface caries and dentin hyperesthesia werenot produced.

EXAMPLE 15

A gel was prepared according to the following formulation using theconventional procedures.

Ingredient Amount (%) Glycerol 30.5 Saccharin sodium 0.1 Polyvinylacetal diethylaminoacetate 0.2 Phosphoric acid 0.1 Flavor 0.1 Sodiumfluoride 1.1 Purified water balance A pH was adjusted to 4.0.

The gel was applied once a month to a part of the tooth surfacedeveloping a white spot using a syringe. After six months, nodevelopment of caries from the white spot was recognized.

EXAMPLE 16

A fluorine varnish for topical application was prepared according to thefollowing formulation using the conventional procedures.

Ingredient Amount (%) Ethanol 60.0 Rosin 20.0 Polyvinyl acetaldiethylaminoacetate 1.0 Phosphoric acid 0.3 Sodium fluoride 2.2 Purifiedwater balance A pH was adjusted to approximately 5.0.

The varnish was applied to a part of the tooth surface developing awhite spot once per two months using a syringe. After one year, thewhite spot was not enlarged and the varnish had an excellentremineralization promoting ability.

As stated above, according to the present invention, a method whichpromotes the remineralization of teeth and has the excellent effects ofpreventing or treating caries or hyperesthesia is provided, by using anoral composition obtained by blending polyvinyl acetaldiethylaminoacetate or an anionic surfactant therein, further byadjusting a pH of the oral composition to 3-6.5.

What is claimed is:
 1. A method of remineralizing teeth which comprisesusing an oral composition comprising polyvinyl acetaldiethylaminoacetate that is blended with a fluoride ion-feeding compoundwhich feeds a fluoride ion.
 2. The method according to claim 1, whereinthe oral composition to be used comprises an anionic surfactant.
 3. Themethod according to claim 1, wherein the pH of the oral composition is3-6.5.
 4. The method according to claim 1, wherein the fluorideion-feeding compound is sodium fluoride.
 5. A method of remineralizingteeth which comprises using an oral composition comprising 0.01-10% byweight of polyvinyl acetal diethylaminoacetate and a fluorideion-feeding compound which feeds a fluoride ion.
 6. The method accordingto claim 5, wherein the pH of the oral composition is 3-6.5.
 7. Themethod according to claim 5, wherein the fluoride ion-feeding compoundis sodium fluoride.
 8. A method of remineralizing teeth which comprisesusing an oral composition comprising 0.01-10% by weight of polyvinylacetal diethylaminoacetate that is blended with a fluoride ion-feedingcompound which feeds a fluoride ion.
 9. The method according to claim 8,wherein the oral composition comprises an anionic surfactant.
 10. Themethod according to claim 8, wherein the pH of the oral composition is3-6.5.
 11. The method according to claim 8, wherein the fluorideion-feeding compound is sodium fluoride.